Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
Authors: Thierry Conroy, Florence Castan, Anthony Lopez, Anthony Turpin, Meher Ben Abdelghani, Alice C. Wei, Emmanuel Mitry, James J. Biagi, Ludovic Evesque, Pascal Artru, Thierry Lecomte, Eric Assenat, Lucile Bauguion, Marc Ychou, Olivier Bouché, Laure Monard, Aurélien Lambert, Pascal Hammel, Eric Francois, Jean-François Ramee, Hélène Castanie, Marc Pracht, François Ghiringhelli, Emmanuel Maillard, Caroline Couffon, Julien Volet, Vincent Bourgeois, Marion Chauvenet, Jean-Frédéric Blanc, Denis Péré-Vergé, Christelle De La Fouchardiere, Antoine Adenis, Farid El Hajbi, Jaafar Bennouna, Patrick Texereau, Roger Faroux, Laurent Miglianico, Christian Platini, Jean-Louis Legoux, François-Xavier Caroli-Bosc, Karine Bouhier-Leporrier, Alice Gagnaire, Victoire Granger, Valérie Lebrun-Ly, Rosine Guimbaud, Yann Touchefeu, Mohamed Gasmi, Frédéric Di Fiore, Jean François Seitz, Pierre-Luc Etienne, Catherine Ligeza Poisson, Yves Rinaldi, Nabil Baba-Hamed, Jean Baptiste Bachet, Thomas Aparicio, Laurence Chone, Marielle Guillet, Julien Forestier, Eric Terrebonne, Mohamed Hebbar, Gilles Breysacher, Thierry Andre, Faiza Khemissa-Akouz, Vincent Hautefeuille, Véronique Guerin-Meyer, Johannes Hartwig, Yves Becouarn, David Malka, Christophe Louvet, Jean-Luc Raoul, Laurent Cany, Beata Juzina, Claire Jouffroy, Sophie Gourgou, Mohammad Rassouli, Haji Chalchal, Daniel Renouf, Ralph Wong, Frederic Lemay, Francine Aubin, Felix Couture, Elaine Mc Whirter, Stephen Welch, Petr Kavan, Brian Findlay, Christine Cripps, Pablo Cano, Shahid Ahmed, Mohammed Harb, Bryn Pressnail, Scott Dowden, Chris O'Callaghan
Journal: JAMA Oncology (2022)

Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available.To report 5-year outcomes and explore prognostic factors for overall survival.This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021.A total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m2 of body surface area; irinotecan, 150-180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 2400 mg/m2, every 2 weeks) or gemcitabine (1000 mg/m2, days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks.Primary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined.Of the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months' follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P < .001) and 5-year disease-free survival was 26.1% vs 19.0%; median overall survival was 53.5 months (95% CI, 43.5-58.4) vs 35.5 months (95% CI, 30.1-40.3) (HR, 0.68; 95% CI, 0.54-0.85; P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P < .001); and median cancer-specific survival was 54.7 months (95% CI, 45.8-68.4) vs 36.3 months (95% CI, 30.5-43.9) (HR, 0.65; 95% CI, 0.51-0.82; P < .001). Multivariable analysis identified modified FOLFIRINOX, age, tumor grade, tumor staging, and larger-volume center as significant favorable prognostic factors for overall survival. Shorter relapse delay was an adverse prognostic factor.The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma.EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135.